Mirko D'Onofrio

Autoimmune Pancreatitis: Differences Between the Focal and Diffuse Forms in 87 Patients

OBJECTIVES:Autoimmune pancreatitis (AIP) is a particular type of chronic pancreatitis that can be classified into diffuse and focal forms. The aim of this study was to analyze clinical and instrumental features of patients suffering from the diffuse and focal forms of AIP.METHODS:AIP patients diagnosed between 1995–2008 were studied.RESULTS:A total of 87 AIP patients (54 male and 33 female patients, mean age 43.4±15.3 years) were studied. Focal-type AIP was diagnosed in 63% and diffuse-type in 37%. Association with autoimmune diseases was observed in 53% of cases, the most common being ulcerative colitis (30%). Serum levels of IgG4 exceeded the upper normal limits (135 mg/dl) in 66% of focal AIP and in 27% of diffuse AIP (P=0.006). All patients responded to steroids. At recurrence non-steroid immunosuppressive drugs were successfully used in six patients. Recurrences were observed in 25% of cases, and were more frequent in focal AIP (33%) than in diffuse AIP (12%) (P=0.043), in smokers than in non-smokers (41% vs. 15%; P=0.011), and in patients with pathological serum levels of IgG4 compared to those with normal serum levels (50% vs. 12%; P=0.009). In all, 23% of the patients underwent pancreatic resections. Among patients with focal AIP, recurrences were observed in 30% of operated and in 34% of not operated patients.CONCLUSIONS:Focal-type and diffuse-type AIP differ as regards clinical symptoms and signs. Recurrences occur more frequently in focal AIP than in diffuse AIP. The use of non-steroid immunosuppressants may be a therapeutic option in relapsing AIP.

Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence

Aim: The aim of this study was to compare contrast-enhanced ultrasonography (CEUS) to baseline US and contrast-enhanced computed tomography (CT) in metastatic disease of the liver diagnosed or suspected by US during presurgical staging or postsurgical follow-up for primary malignancies. Materials and methods: Two hundred-fifty-three patients considered suitable for US due to the complete explorability of the liver and with one to five proven or suspected liver metastases at baseline US were included. All patients underwent US before and after microbubble injection, and multiphase contrast-enhanced CT. Independent panels of readers reviewed US and CT scans and recorded liver metastases according to a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance) and area under the receiver operating characteristics (ROC) curve (diagnostic confidence) were calculated. Results: Reference standards revealed no metastases in 57/253, more than five in 59/253, and one to five in 137/253 patients. In patients with one to five metastases, CEUS versus baseline US revealed more metastases in 64/137 and the same number in 73/137 patients while CEUS versus CT revealed more metastases in 10/137, the same number in 99/137, and lower number in 28/137. Sensitivity, specificity, and area under ROC curve of CEUS (83%, 84%, 0.929, respectively) differed from baseline US (40%, 63%, 0.579, respectively; P 0.05). Conclusion: CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.

Tissue Quantification With Acoustic Radiation Force Impulse Imaging: Measurement Repeatability and Normal Values in the Healthy Liver

OBJECTIVE The purpose of this study was to describe the most reliable measurement procedure for acoustic radiation force impulse technology and to define the normal wave velocity values in a healthy liver. SUBJECTS AND METHODS Twenty healthy volunteers underwent acoustic radiation force impulse imaging tissue quantification and were enrolled in this prospective study. All patients were examined by two independent operators at the same time. Twenty-four measurements per subject were obtained. Intraoperator and interoperator evaluations were performed. Statistical comparison of all mean data was performed with Students t test. A value of p < 0.05 was considered significant. A comparative analysis was performed, and interclass correlation coefficients were calculated. RESULTS The operators obtained 960 measurements. A statistically significant difference was found between the mean shear wave velocity values obtained by one operator deep in the right lobe of the liver and the values obtained on the surface of the right lobe (1.56 vs 1.90 m/s) and between the mean values obtained deep in the right lobe and those obtained deep in the left lobe (1.56 vs 1.84 m/s). The other operator had similar results. The distribution of all mean values obtained by both operators deep in the right hepatic lobe exhibited less dispersion (95% CI, 1.391-1.725) than those obtained on the surface (95% CI, 1.664-2.136). In 77.5% of cases, the shear wave speeds were between 1 and 2 m/s. No statistically significant difference was found in the comparisons performed on the right hepatic lobe by the two operators. The interclass correlation coefficient calculated for measurements deep in the right lobe was 0.87 (p < 0.0001). CONCLUSION Acoustic radiation force impulse imaging quantification of hepatic tissue is more reproducible when applied to the deeper portion of the right lobe of the liver.

Acoustic Radiation Force Impulse Elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study

AIM The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. PATIENTS AND METHODS We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5-10 valid measurements, expressed in meters/second - m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6-10 valid measurements, expressed in kiloPascals - kPa). RESULTS Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r=0.654) was found between ARFI measurements and fibrosis (p<0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 - cut-off>1.19 m/s (AUROC=0.779), F ≥ 2 - cut-off>1.33 m/s (AUROC=0.792), F ≥ 3 - cut-off>1.43 m/s (AUROC=0.829), F=4 - cut-off>1.55 m/s (AUROC=0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r=0.728 vs. 0.689, p=0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p=0.01) and fibrosis (F ≥ 1, METAVIR) (p=0.01). CONCLUSION ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography.

PURPOSE VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good.

Observational Study of Natural History of Small Sporadic Nonfunctioning Pancreatic Neuroendocrine Tumors

CONTEXT Asymptomatic sporadic nonfunctioning, well-differentiated pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. OBJECTIVE The objective of the study was to assess the natural history of asymptomatic sporadic NF-PNETs smaller than 2 cm in size and the risk-benefit balance of nonoperative management. EXPERIMENTAL DESIGN From January 2000 to June 2011, 46 patients with proven asymptomatic sporadic NF-PNETs smaller than 2 cm in size were followed up for at least 18 months with serial imaging in tertiary referral centers. RESULTS Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range 9-15). After a median follow-up of 34 months (range 24-52) and an average of four (range 3-6) serial imaging sessions, distant or nodal metastases appeared on the imaging in none of the patients. In six patients (13%), a 20% or greater increase in size was observed. Overall median tumor growth was 0.12 mm per year, and neither patients nor tumor characteristics were found to be significant predictors of tumor growth. Overall, eight patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range 27-58); all resected lesions were European Neuroendocrine Tumor Society T stage 1 (n = 7) or 2 (n = 1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. CONCLUSIONS In selected patients, nonoperative management of asymptomatic sporadic NF-PNETs smaller than 2 cm in size is safe. Larger and prospective multicentric studies with long-term follow-up are now needed to validate this wait-and-see policy.

Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response.

BACKGROUND AND AIMS:Many staging systems for hepatocellular carcinoma (HCC) have been proposed but the best tool for staging of HCC remains controversial. The aim of the present study was to identify the best staging system evaluating the predictive ability for outcome for each of the seven different staging systems applied in a homogeneous group of patients who underwent percutaneous radiofrequency ablation (RFA).METHODS:We analyzed retrospectively 112 patients with HCC and cirrhosis treated with percutaneous RFA from January, 1998 to April, 2005. Response to treatment after 30 days and for long-term follow-up was evaluated with computed tomography (CT) or magnetic resonance imaging (MRI) and serum alpha-fetoprotein level (AFP). All of the 112 patients were grouped according to each one of the seven different staging systems: Okuda, TNM, BCLC, CLIP, GRETCH, CUPI, JIS.RESULTS:The mean follow-up time of the 112 patients submitted to RFA was 24 months (range 3–92 months) with survival rates at 1, 3, and 5 yr of 82%, 40%, and 18%, respectively. Univariate and multivariate analyses showed that factors related to survival were Child-Pugh score (P ≤ 0.01), serum AFP (P ≤ 0.01), and the response to treatment (P ≤ 0.01) with hazard ratios of 2.09 (95% CI 1.21–3.61), 2.79 (95% CI 1.59–4.90), and 2.76 (95% CI 1.25–6.09), respectively. The comparison of the results of the different staging systems in all of the 112 patients and in a subgroup of 96 patients with complete response to treatment showed that BCLC had the best discrimination ability, monotonicity of gradient (linear trend χ2 6.07, P = 0.01), and homogeneity ability (LR χ2 test 10.00, P = 0.008).CONCLUSIONS:The BCLC staging system shows a superior discriminatory power in our cohort of HCC patients who underwent RFA; moreover, it can give important prognostic information after complete response to treatment. Our study confirms the validity of the BCLC staging system in patients with HCC in cirrhosis.

Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy

BACKGROUND Neoadjuvant treatment frequently is performed in unresectable/borderline resectable pancreatic cancer. The aim of this study was to retrospectively compare postoperative outcomes and survival of patients who underwent pancreatectomy after neoadjuvant treatment for locally advanced/borderline resectable pancreatic cancer (neoadjuvant treatment group) with those of patients with resectable disease who underwent upfront surgery. METHODS Between 2000 and 2008, there were 403 patients who underwent pancreatic cancer resection, 41 (10.1%) patients after neoadjuvant treatment for initially unresectable tumors and 362 (89.9%) patients had upfront surgery. Univariate and multivariable analyses were performed. RESULTS Mortality/morbidity rates were similar in the 2 groups. Nodal metastases were significantly lower in the neoadjuvant treatment group (31.7% vs 86.2%; P < .001). A complete pathologic response was observed in 13.6% after neoadjuvant treatment. Median disease-specific survival from resection was 35 and 27 months in the neoadjuvant treatment and upfront groups, respectively (P = .74). In the neoadjuvant treatment group survival rates were similar in N0/N1 patients. CONCLUSIONS Postoperative mortality and morbidity do not significantly increase after neoadjuvant treatment. Neoadjuvant treatment in locally advanced pancreatic cancer can lead to an objective pathologic response, but this does not significantly improve survival after resection.

Comparison of contrast-enhanced sonography and MRI in displaying anatomic features of cystic pancreatic masses.

OBJECTIVE The purpose of this study was to compare the accuracy rates of unenhanced sonography, contrast-enhanced sonography, and MRI in displaying the anatomic features of cystic pancreatic masses larger than 1.5 mm in diameter. MATERIALS AND METHODS Unenhanced and contrast-enhanced sonographic and MRI examinations of 33 patients who underwent resection of a cystic pancreatic mass were retrospectively reviewed. Two radiologists blinded to the final histologic diagnosis reviewed the images, specifically assessing the presence of intralesional mural nodules and septa. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated on the basis of correlation with surgical findings. Results of unenhanced sonography, contrast-enhanced sonography, and MRI were compared by McNemar test. Correlation of unenhanced and contrast-enhanced sonographic versus pathologic results was established with Spearmans test. Interobserver variability was determined. RESULTS Contrast-enhanced sonography correctly depicted intralesional septa in 14 of 15 lesions (sensitivity, 93.3%; specificity, 88.8%; positive predictive value, 87.5%; negative predictive value, 94.1%; accuracy, 90.9%) and nodules in six of eight lesions (sensitivity, 75%; specificity, 96%; positive predictive value, 85.7%; negative predictive value, 92.3%; accuracy, 90.9%). MRI correctly depicted intralesional septa in 14 of 15 lesions (sensitivity, 93.3%; specificity, 61.1%; positive predictive value, 66.6%; negative predictive value, 91.6%; accuracy, 75.7%) and nodules in seven of eight lesions (sensitivity, 87.5%; specificity, 80%; positive predictive value, 58.3%; negative predictive value, 95.2%; accuracy, 81.8%). The difference between the diagnostic accuracy of contrast-enhanced sonography and that of MRI was not significant (p = 0.05, McNemar test) in the identification of septa and nodules. The correlation between contrast-enhanced sonographic findings and pathologic results (Rs = 0.93; p < 0.001) was significantly better than that between sonographic and pathologic results (Rs = 0.52; p < 0.0001). Interobserver agreement had a kappa value of 0.86-0.94. CONCLUSION Contrast-enhanced sonography compares favorably with MRI in displaying the anatomic features of cystic pancreatic masses seen on transabdominal sonography.

Contrast-enhanced sonography of nonfunctioning pancreatic neuroendocrine tumors.

OBJECTIVE Diagnosis of malignancy and prognostic assessment continue to be problems in the management of nonfunctioning pancreatic endocrine tumors. Histologic examination is the reference standard. The aim of our study was to compare B-mode and contrast-enhanced sonographic findings regarding nonfunctioning pancreatic endocrine tumors. Signs of malignancy, such as Ki67 index and presence of hepatic metastasis, were considered. MATERIALS AND METHODS We retrospectively reviewed the cases of 38 consecutively registered patients with nonfunctioning pancreatic endocrine tumors evaluated with B-mode and contrast-enhanced sonography and resected. At contrast-enhanced sonography all lesions were divided into hypovascular lesions and isovascular or hypervascular lesions. On the basis of homogeneity of enhancement, lesions were classified as homogeneous and inhomogeneous. During the late phase of contrast enhancement, all solid focal hypoechoic liver lesions detected at contrast-enhanced sonography were considered hepatic metastatic lesions. Among pathologic data, grading, mitotic index, and Ki67 index were evaluated. Spearmans test was used to compare contrast-enhanced sonographic enhancement pattern with pathologic grade. RESULTS In the arterial phase, 24 of 38 nonfunctioning pancreatic endocrine tumors (63.1%) were hypervascular, seven (18.4%) were isovascular, and seven (18.4%) were hypovascular. Positive correlation was found between contrast-enhanced sonographic findings and Ki67 index (r(s) = 0.62; p < 0.0001). The difference between contrast-enhanced and B-mode sonography in the diagnosis of nonfunctioning pancreatic endocrine tumors was statistically significant (p < 0.05). Use of contrast-enhanced sonography increased diagnostic confidence in the detection of hepatic metastasis. The areas under the receiver operating characteristic curves were 0.916 for B-mode sonography and 1.000 for contrast-enhanced sonography (p < 0.05). There was moderate positive correlation between contrast-enhanced sonographic enhancement pattern and the presence of hepatic metastasis at diagnosis (r(s) = 0.46; p = 0.004) and between Ki67 index and the presence of hepatic metastasis (r(s) = 0.48; p = 0.0022). CONCLUSION The contrast-enhanced sonographic enhancement pattern of nonfunctioning pancreatic endocrine tumors has a positive correlation with Ki67 index, which is considered the most reliable independent predictor of the presence of malignancy.